Hypertrophic cardiomyopathy is the most common inherited heart disease and is the most important cause of sudden death in the young. Recently, a gene which controls the production of the main protein of the heart, beta myosin heavy chain gene, located on chromosome 14, has been linked to the disease in some kindreds with hypertrophic cardiomyopathy, We have found distinct mutations in the beta myosin heavy chain gene in several kindreds with hypertrophic cardiomyopathy. We have also shown that although the disease affects the heart predominantly, the cardiac protein is also expressed in skeletal tissue and that the mutant RNA and protein are also to be found in skeletal muscle. This has led us to determine whether the single myofibers in skeletal muscle has abnormal mechanical function. Isometric tension generated by single skinned soleus muscle fibers was measured in affected individuals with identified mutations. This was significantly reduced in several patients with a mutation (403ArgGln) associated with a malignant prognosis but not in other mutations. This suggests that hypertrophic cardiomyopathy patients with distinct mutations in the cardiac beta myosin heavy chain gene may have skeletal muscle with abnormal mechanical properties and that the pathophysiology of the disease is varied at a cellular and molecular level.